By Day 1 of Week Five, the instructor will send you two de-identified grant proposals to review for this assignment . You will play the role of a grant reviewer by reading and giving feedback to two o

The Effect of Anesthesia and Alzheimer a Post-Operative Cognitive Dysfunction of the Aging Population

Student C

PSY625: Biological Bases of Behavior

Instructor: Nikola Lucas

September 10, 2018

The Effect of Anesthesia and Alzheimer a Post-Operative Cognitive Dysfunction of the Aging Population

Specific Aims

Any form of surgery that is major and is inclusive of a general anesthetic (e.g. heart conditions, hip or knee replacements), is standard for many adults who are elderly. There is great risk following general anesthesia for the development of continual problems that goes past the period of short term perplexity which takes place after surgery. This disorder that is long-lasting is what is called post-operative cognitive decline which is believed to be related to the swelling or inflammation within the brain and resembles that which is seen in the disease known as Alzheimer’s. Due to posing a high risk to the aging population, there is an urgent need of understanding the way in which this cognitive decline evolves and find ways of preventing it. As a common form of dementia, Alzheimer is considered to reach at least 26.6 million individuals nationwide, or at least around five percent of the 65 and older population (Arora, Gooch, & García, 2014).

The aim of this proposal is to provide clinical awareness into Postoperative Cognitive Dysfunction (POCD) and the relationships between general anesthesia, surgery, Alzheimer’s Disease. Also, comprehending the way in which to manage AD patients of the aging population is of great significance as we prepare to care for the increase in elderly patients during the period in which they are in a perioperative stage. Upon investigating the possible cognitive effects of anesthesia, it is extremely important to begin by looking at the differences between dementia and delirium. Although both illnesses share symptoms that are similar, such as mood swings, issues with perception, reduced cognition, and confusion, one critical differentiates them. Dementia is described as a moderate decline of cognitive abilities which is permanent, while delirium is an abrupt, but temporary change in an individual’s mental functioning. Individuals that develop dementia can show indications of delirium, however, these two terms are not transposable (Wan & Chase, 2017).

There is also an approximation of 5.5 million individuals in America that are suffering from AD with age being the primary risk factor. It has also been determined that after the age of 65, the prevalence of the diagnosis of AD is doubled by every five years e.g. Arora, Gooch, & García, (2014). Also, along with the other health considerations, the surgical aging patients continue to increase and most likely have AD that was pre-existing, or they are at a risk of developing Alzheimer Disease. There has been a popular interest shown that is geared towards determining the way in which anesthesia impacts the progression or development of Alzheimer Disease. Likewise, there is no current best practice for patients with AD regarding anesthetic management (Arora, Gooch, & García, 2014). In addition, the association between Alzheimer Disease and the vulnerability to or provocation of post-operative cognitive dysfunction is not fully understood as of today. Randomized clinical studies that are long-term are needed to examine the link between AD and POCD.

Background

Typically considered effective and safe, anesthetic drugs presented us with significant benefits clinically. With the continued nationwide acceleration of the ageing population, surgeries are performed on a frequent basis. However, there continues to be increasing concerns that either surgery or anesthesia could have complications that are neurodegenerative. Patients who have Alzheimer’s Disease also known as (AD), have appeared to be extremely susceptible to cognitive decline after procedures requiring anesthesia. There are also studies which suggest that being exposed to anesthetics could heighten the risk of Alzheimer’s Disease.

There has been great concern in the regards to the elderly population and the ramifications on cognition from anesthesia used for surgery. When it comes to cognitive disorders like that of post-operative cognitive dysfunctions, delirium, and confusion which are typical in the elderly following anesthesia, symptoms tend to persist in some patients for months or years (Papon, Whittington, El-Khoury, & Planel, 2010). The study review literature links AD to anesthesia and are focusing upon the biochemical reactions of anesthesia exposure of the pathogenic pathways of AD. More research to help with Identifying the relationship between AD and post-operative cognitive decline is of significance when it comes to finding procedures, alternative anesthetics, and managing POCD for the aging population suffering with cognitive declines which hinders their ability to having a life that is fulfilling and productive.

There have been many studies utilizing a design that was case controlled that have analyzed anesthesia exposure during surgery as a possibility for incidental dementia. As outlined in a current meta-analysis, there was a small amount of evidence which showed that being exposed to general anesthesia during surgical as well as other procedures are separate risk factors for dementia (Sprung, et al., 2013). However, the studies that are available also have limitations that are notable, this is inclusive of small sample sizes which limits statistical power, selection of appropriate controls, selection biases in the construction of case cohorts, small amount, if any information at all regarding details of exposure to anesthesia.

The current study aimed at mitigating the limitations through the usage of Rochester Epidemiology Project that allows access to each of the residents of Olmsted County, Minnesota health records; and the Alzheimer’s Patient Registry at the Mayo Clinic, which also includes every incident case of dementia from 1985 to 1994 in Olmsted County; as well as the sex and age and sex matching cohorts that do not include Dementia during the time of the index diagnosis ( Sprung, et al., 2013). The main objective was to analyze the hypothesis that being exposed to general anesthesia is not significantly related with incident dementia after age 45 utilizing a design that is a case-controlled study.

This study’s main finding was that, after the age of 45 inhaling general anesthesia needed for a procedure does not place the participant at risk for incident dementia. However, the concerns related to the possible effects of surgery and anesthesia on postoperative cognition have risen from two main sources. Even though cognition is accepted could be affected during the postoperative time frame, there are a few authors who have proposed that an increased POCD

could be relatively typical and it is a public health concern that is serious (Sprung, 2013). In this review, the authors established that today’s evidence is not convincing that surgery and anesthesia are related to long-term dementia or POCD and they pointed out several barriers in researching this area, along with the undersupply of diagnostic standards for POCD; division of any single effects of anesthesia from those related to surgical stress, ageing, the possible role of cognitive impairment that preexisted, multiple possible confounding elements which makes the selections of proper controls in a study significant. Secondly, when tested on older rodents through in vitro and in vivo, the findings called for hypothesizing that anesthesia could begin or speed up processes which could lead to AD or the progression of it (Sprung, 2013).

However, from another perspective, performing a systematic review that included the evidence available was done by the guidelines of PRISMA. There was also a search done utilizing; PubMed, LILACS, EMBASE, Grey Literature Reports, Clinical Trials, and Scielo in 2017 from May through July. Included criteria was studies of prospective design that had patients who were over the age of 18, surgery that included regional and general anesthesia, utilized as well as a three-month follow-up and was diagnosed through the usage of a neurocognitive battery (Paredes, Cortínez, Contreras, & Silbert, 2016). The authors did not use studies that included brain surgery and cardiac patients. The authors also selected twenty-four studies and sixty-eight years old was the average age. There were just 5 studies that made a report of incidence of cognitive declines for a control group that was non-surgical. The median numbers of the test utilized were 5 and the pooled occurrence of POCD at three months were 11.7 percent, but it was with many methodological variations among the studies.

Further, the risk factor which was identified and was the most consistent in seven studies was age. Also, the authors of this study, found that POCD appears to be frequent in patients, predominately when the patients are over the age of sixty. The limitations included methodological variations in the studies. However, efforts are critical when it comes to reaching a consensus in the diagnosis and definition for research in the future. In addition to the compilation of evidence that proves that there is cause for concern when it comes to the aging population, anesthesia. and POCD, Kilaru, et al., (2018), designed and performed a study on the population of elderly Indians who were undergoing a complete knee replacement after being given spinal anesthesia.

The study designed was observational and was at a independent center inclusive of patients who were over the age of sixty. There were preoperative measures taken that involved a mini-mental scale assessment, creatine and urea levels as well as, electrolytes were recorded. The POCD consisted of an MMSE which was performed two days after the surgery, three months, six months and one-year follow-ups and postoperatively the laboratory values were then recorded. The average of the preoperative MMSE was at 27 and dropped to around 25.4 on the second day of postop the value then increased to 25.9, 26.6, and 27 by month 3, month six and one-year follow-ups (Kilaru, et al., 2018). Out of the six-hundred patients, there 63 that had developed Postoperative Cognitive Dysfunction by the second day. There were 43 that exhibited recovery later in follow-ups, and twenty continued to have dysfunction by the end of the one-year period. In their study, the authors found that POCD is a positive entity that could cause long and short -term cognitive defects in the elderly population of Indian’s who underwent complete knee replacement and that age, oxygen saturation, and electrolyte imbalances were major factors in the patients that had developed POCD (Kilaru, et al., 2018).

In a study performed on 90 patients ranging from the age of 65 to 75, who were scheduled to have a esophageal carcinoma resection and were assigned randomly to one out of the three groups in accordance: Group labeled as S+MP received preoperative methyl prednisone prior to being administered sevoflurane anesthesia, another group listed as Group C, was a control group and was given intravenous Propofol, and lastly would be Group S, which was provided with an sevoflurane (Qiao et al.2015). These studies in elderly people would provide evidence that POCD was higher in elderly individuals who are having a major surgery and are being administered inhaled anesthesia containing sevoflurane than the ones who were provided with intravenous Propofol, and it was lesser in those patients who were pretreating with the methyl prednisone.

The research provided by Steinmetz, et al., (2010), also reviews evidence related to POCD and the aging population and the effect of anesthesia on the cognitive function of those undergoing surgical procedures. There were 460 patients who were age seventy and had been scheduled for elective surgery that was not related to cardiac surgery with general anesthesia. The anesthesia depth had been monitored through the utilization of the cerebral state monitor that would provide a cerebral state index value (Steinmetz, et al., 2010). The ISPOCD neuropsychological test battery was utilized to assess the cognitive functions prior to and one week after the surgery, Postoperative Cognitive Dysfunction had been determined to be a Z

score that was over 1.96. As a result, it was concluded that five of the patients were not evaluated at the end of the surgery. The CSI mean in patients was 40 and 43without and with POCD. The time cumulated between light and deep anesthesia were not significantly different, and there were no major correlations found among the Z and CSI score. The study was not able to detect a major link between the anesthesia depth and the presence of POCD seven days after surgery.

Significance

The research being proposed will utilize an observation study centered around a small aging population. Taking into consideration all the literature available, it is necessary that further perioperative understandings are needed regarding the issues linked to anesthesia which could assist with enhancing the results, lowering the morbidity of the methods being utilized. Lower physiological reserve impaired the ability of the body in this group to sustain homeostasis while in the periods of stress, which lead to cognitive and physical dysfunctions which resulted in perioperative problems that were severe. Making a choice to use anesthesia should also be assessed on basis that is case by case and customized to the health status of each patient, the kind of operation, patient’s medications and coexisting diseases to provide the most productive perioperative treatment. There is a need for new methods which could provide procedures that are minimally invasive, has lesser morbidity which increases safety, specifically in patients that are high risk. In the future, a larger group of patients that are elderly will have to undergo anesthesia, this is not just because of the increased population, but increased probabilities related to age that an individual has to a need for procedures requiring surgery.

Proposed Study

Participants:

This will be a controlled randomized trial study, which will include 60 recruited participants who are over the age of 65 and are cognitively healthy as exhibited in comprehensive neuropsychological assessment (Di Pucchio, et al., 2018) tests and prior to surgical procedures (e.g. hip surgery, abdominal surgery) where inhaled anesthesia is administered and conducted at the Brain Center of Haverty’s School of Medicine where the patients will be divided into two Groups (e.g. A & B).

The patients will be provided with general educational material about their surgery and will then be asked to continue their normal daily duties as they would usually do until the day they are admitted for surgery. This part will be performed by the nurses who are from the medical facility where the surgery will be conducted but are not taking part in the study.

Procedures:

Patients will then be provided with a nutritional assessment during the intervention part of the study which will be administered in proper accordance following the nutritional procedures (e.g. appendix B online supplementary, and if necessary, nutritional supplements will also be prescribed). An online cognitive exercise will be provided in the format of games involving memory cards, which will be taught to the caregivers if they are available and the patients, and the memory game will be utilized twice a day. There will be research assistants and dieticians that are related to the study who will perform the cognitive interventions, physiotherapy, and nutritional aspects of the study.

The intervention will be running for 30 days where the patient will choose the sessions in which they want to participate in. Although, there is no consensus based on the amount of time involving pre-rehabilitation that is needed for optimizing surgical patients, in other studies, done previously the amount of time would range from two to four weeks. However, it has been hypothesized that through the combining of various interventions into bundles, we could possibly reach effects that are beneficial within a time frame that is shorter. Taking into consideration that it could take as long as three days for patients to be seen in the preoperative assessment clinic, be signed up for the study and be provided with the intervention, a ten-day pre-rehabilitation timeframe of ten days to be achievable and pragmatic. The participating patients will also be supplied with supplementary appendix methods activities logs and there will be a research assistant that will be conducting a series of conversations by telephones and live chat on days two, four, and eight, to encourage and ensure that the patients are complying with protocol and will be answering any queries regarding the study.

A brief and structured test referred to as the Mini- Mental State Exam will be utilized to test the mental status of patients. The MMSE takes approximately ten minutes for completion. This exam was established by, Marshall Folstein as well as others during 1975 and is one of the most widespread utilized test in assessing complications with the several cognitive functions and the memory (Sheehan, 2012). The specificity and sensitivity of the Mini-Mental State Exam, primary properties of each screening assessment, are justifiably good. Another significant utilization of the MMSE would be using it to evaluate cognitive variations in a patient over time. Testing done periodically using the MMSE could be helpful in assessing the participant’s responses to treatment, which would be helpful with guiding treatments in the future.

Hypothesis & Analysis:

The main objective of this study is assist with determining whether pre-rehabilitation inclusive of bundles of interventions (general educational materials, cognitive exercises and nutritional support) provided before surgery in patients that are undergoing elective hip or abdominal surgery will conclude in the patient being cognitively impaired and the time span of the patient’s cognitive impairment. The second objective is determining if pre-habilitation will lower postoperative issues and enhance the patients cognitive and functional recovery after surgery. Upon the day of surgery, the recovery of the patients after surgery will be evaluated utilizing what is known as the PQRST, which is a method used to assess pain, it is a significant tool which correctly describes, assess and documents the pain of a patient.

The procedure also assists with selecting the appropriate type of pain medicines and assessing the patient’s responses to treatment (Crozer Keystone, n.d.). Repetition of the PQRST scale will then be administered to measure the recovery of the patient from their surgery to assess their discharge from the Post Anesthetic Care Units and the scale will then be repeated on days 2,4, and 8 of postoperative. There will then be an assistant involved in the research that will be designated with examining the clinical files of the patients for a list of any problems every other day until after the patient is released or up to at least thirty days after their surgery.

At any time, those participating in this study will be allowed to remove themselves from participation in the study. Demographical information of patients who are eligible but declined to participation as well as the patients whom withdraw their consent after randomization will be collected also as to assess the practicality and the adopting rate of the intervention bundles. Although the patients do not have to provide a valid reason for leaving the study, their reasons for withdrawing will still be registered. There will be paper as well as electronic records which will be utilized to acquire data on the demographics of the patients, anesthetic variables, dementia/delirium, infections, urgency of procedure, intraoperative procedures.

Budget Justification

Funding is being requested for a research assistant that will have the responsibility of each facet of recruiting subjects, collection of data and training, Additional allowances of ten % are also being requested for the individual known as the principal investigator. The PI will supervise the study as well as conduct the analysis of data and results of publication. Funding for traveling is also requested for the principal investigator to frequent at least one national conference at which to do a presentation of the explorative findings of the study. Further funds are needed for transportation expenditures by the assistant researcher to the demographical locations of each of the homes of the subjects. Subject payments of $60 per subject totaling 60, is also requested to compensate the participation time of each subject.

A request for funding of an HP Envy x360 (15” with Intel core I5 processor, 1 terabyte hard drive, micro edge full HD IPS touch display, four modes and windows ink) which will be utilized to collect and analyze data.

Further funding is also needed for purchasing office supplies and PQRST, the MMSE programs.

See Appendix A: Budget for detailed budget figures.

References

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Baumann, S. L. (2017). Postoperative Cognitive Decline: The State of the Science. MEDSURG Nursing, 26(6), 378-385.

Bittner, E. A., M.D., Yue, Y., M.D., & Xie, Z., M.D. (2011). Brief review: Anesthetic neurotoxicity in the elderly, cognitive dysfunction and Alzheimer’s disease. Canadian Journal of Anesthesia, 58(2), 216-23. doi: http://dx.doi.org.proxy-library.ashford.edu/10.1007/s12630-010-9418-x

Crozer Keystone Health System (n.d.) PQRST Pain Assessment Method. Retrieved 09/10/2018 from http://www.crozerkeystone.org/healthcare-professionals/nursing/pqrst-pain-assessment-method/

Di Pucchio, A., Vanacore, N., Marzolini, F., Lacorte, E., Di Fiandra, T., I-DemObs Group, & Gasparini, M. (2018). Use of neuropsychological tests for the diagnosis of dementia: a survey of Italian memory clinics. BMJ Open, 8(3), e017847. http://doi.org/10.1136/bmjopen-2017-017847

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Kilaru, P., Reddy, A., Reddy, M., Kidiyoor, B., Joseph, V., & Reddy, A. (2018). Postoperative cognitive dysfunction in Indian patients undergoing total knee replacement under spinal anesthesia. Anesthesia: Essays and Researches, (1),

Mason, S. E., Noel-Storr, A., & Ritchie, C. W. (2010). The Impact of General and Regional Anesthesia on the Incidence of Post-Operative Cognitive Dysfunction and Post-Operative Delirium: A Systematic Review with Meta-Analysis. Journal Of Alzheimer's Disease, 2267-79. doi:10.3233/JAD-2010-101086

Papon, M.-A., Whittington, R. A., El-Khoury, N. B., & Planel, E. (2010). Alzheimer’s Disease and Anesthesia. Frontiers in Neuroscience, 4, 272. http://doi.org/10.3389/fnins.2010.00272

Paredes, S., Cortínez, L., Contreras, V., & Silbert, B. (2016). Post-operative cognitive dysfunction at 3 months in adults after non-cardiac surgery: a qualitative systematic review. Acta Anaesthesiologica Scandinavica, 60(8), 1043. doi:10.1111/aas.12724

Qiao, Y., Feng, H., Zhao, T., Yan, H., Zhang, H., & Zhao, X. (2015). Postoperative cognitive dysfunction after inhalational anesthesia in elderly patients undergoing major surgery: the influence of anesthetic technique, cerebral injury and systemic inflammation. BMC Anesthesiology, (1), doi:10.1186/s12871-015-0130-9

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Sprung, Juraj, M.D., PhD., Jankowski, C. J., M.D., Roberts, R. O., M.D., Weingarten, T. N., M.D., Aguilar, A. L., S.R.N.A., Runkle, K. J., S.R.N.A., . . . Warner, D. O., M.D. (2013). Anesthesia and incident dementia: A population-based, nested, case-control study. Mayo Clinic Proceedings, 88(6), 552-61. Retrieved from https://search-proquest-com.proxy-library.ashford.edu/docview/1371443636?accountid=32521

Steinmetz, J., Funder, K.S., Dahl, B.T., & Rasmussen, L.S. (2010). Depth of anesthesia and post-operative cognitive dysfunction. Acta Anaesthesiologica Scandinavica, 54(2), 162. doi:10.1111/j.1399-6576.2009. 02098.x

Wan, M., & Chase, J.M., (2017). Delirium in older adults: Diagnosis, prevention, and treatment. BCMedical Journal. Issue: BCMJ, vol. 59, No. 3, April 2017, Pages 165-170 Clinical Articles. Retrieved 9/10/2018 from https://www.bcmj.org/articles/delirium-older-adults-diagnosis-prevention-and-treatment

Appendix A: Budget